Several clinical subtypes of AD have been proposed; the variable rate of deterioration also implies the existence of benign and malignant forms. The neurologic and psychiatric symptoms (myoclonus, parkinsonism, depression, and psychosis) associated with the clinical presentation of AD are also paralleled by the neuropathological variations in the expression of the disease. while the validity of any of these clinical subtypes is unclear, theories on the etiology of AD need to address the possibility that different forms of the disease exist and are caused by different combinations of genetic and environmental factors, as well as by the deficiencies of various trophic factors. The systematic compilation and analysis of brain and other post-mortem tissues from aD cases is a first step in attempting a clinico-pathological correlation. Such studies will identify which of the cellular alterations in AD are nonspecific and which are primarily characteristic of the disorder. The tissue repository should thus facilitate studies leading to the construction of comprehensive theories on the pathophysiology of AD. These studies should also significantly advance our understanding of the role of abnormal genes in AD, leading to the identification of new biological markers for this degeneration. The long term objectives of the neuropathology core are to obtain and store brain issue and other biological specimens from AD and circulatory demential (CD) patients enrolled in the longitudinal study and from controls for use in current and future research projects. Tissues from all, or all possible patients, who have been studied in the center will be analyzed at death. Neuropathological confirmation of diagnosis will thus be obtained. Specimens will also be made available to other centers for other special studies as new probes or techniques are developed. Autopsy will be performed as soon as possible after death. Standardized protocols for tissue processing will not only enable morphological studies to confirm the diagnosis, but also quantitate the extent of neuronal cell loss and the distribution and density of senile plaques and neurofibrillary tangles. Biochemical studies on serial adjacent frozen slices will quantitate changes in neurotransmitter and peptide levels. The data on brain and general autopsy will be entered into coded spread sheets checked for accuracy and completeness. This information will be sent to the data management core for entry. Another long term objective is to facilitate the use of new immunological and molecular probes in normal aging brains as well as in AD and CD brains.